The present invention relates to novel substituted derivatives of 4-(1H-pyrrol-1-yl)imidazoles which are useful as pharmaceutical agents, to methods for their preparation, to pharmaceutical compositions which include the compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment as well as the use of these agents as diagnostic tools. The novel compounds of the present invention are antagonists of angiotensin II (AII) useful in controlling hypertension, hyperaldosteronism, congestive heart failure, atherosclerosis, postsurgical vascular restenosis, renal failure, and glaucoma in mammals.
The enzyme renin acts on a blood plasma .alpha..sub.2 -globulin, angiotensinogen, to produce angiotensin I, which is then converted by angiotensin converting enzyme to AII. The latter substance is a powerful vasopressor agent which has been implicated as a causative agent for producing high blood pressure in various mammals, such as rats, dogs, and humans. Angiotensin II has also been found to stimulate vascular hyperplasia as reported by W. Osterrieder, et al (Hypertension 18[suppl II]:II60-II64, 1991); H. Azuma, et al (Jpn. J. Pharmacol. 52(4):541-552, 1990); and S. Laporte, et al (FASEB 5(4), Part I: A869, 1991). The compounds of this invention inhibit the action of AII at its receptors on target cells and thus prevent the increase in blood pressure produced by this hormone-receptor interaction. By administering a compound of the instant invention to a species of mammal with hypertension due to AII, the blood pressure is reduced. The compounds of the invention are also useful for the treatment of congestive heart failure, hyperaldosteronism, atherosclerosis, postsurgical vascular restenosis, and glaucoma.
European Patent Application 0253310 discloses angiotensin II receptor blocking imidazoles of the formula ##STR1##
European Patent Application 0291969 disclose tetrazole intermediates to antihypertensive compounds ##STR2##
European Patent Application 401030 discloses substituted imidazo-fused seven-member ring heterocycles of Formulae I and Ia ##STR3## which are useful as angiotensin II antagonists.
WO 91/00277 discloses substituted imidazoles useful as angiotensin II blockers ##STR4##
However, the compounds disclosed in the above references do not disclose or suggest the novel combination of structural variations found in the compounds of the present invention described hereinafter.